Pathological tau signatures and nuclear alterations in neurons, astrocytes and microglia in Alzheimer's disease, progressive supranuclear palsy, and dementia with Lewy bodies.
Pathological tau signatures and nuclear alterations in neurons, astrocytes and microglia in Alzheimer's disease, progressive supranuclear palsy, and dementia with Lewy bodies.
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DOI：
10.1111/bpa.13112
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发表时间：
2023-01
期刊：
影响因子：
6.4
通讯作者：
Kayed, Rakez
中科院分区：
文献类型：
--
作者：
Montalbano, Mauro;Majmundar, Lajja;Sengupta, Urmi;Fung, Leiana;Kayed, Rakez
病理性tau聚集物的堆积是tau病的一个显著特征，在疾病过程中会导致神经元功能障碍和细胞死亡。小胶质细胞和星形胶质细胞在多种神经退行性疾病(NDS)中毒性tau的突触扩散中发挥重要作用。在这里，我们研究了tau诱导的神经退行性疾病(如阿尔茨海默病(AD)、进行性核上性麻痹(PSP)和路易体痴呆(DLB))中不同脑细胞类型中聚集的tau的免疫学和生化特性。此外，我们还检查了病变脑组织中神经元和神经胶质细胞的核大小、核密度和染色质致密程度。用小鼠体内针对毒性tau构象(TTC-M1和TTC-M2)和tau寡聚体(TOMA1-4)的单抗进行显微组织学检查。通过Toma/TTC-ms和神经元、星形胶质细胞和小胶质细胞的细胞类型特异性标记的免疫组织化学和联合免疫荧光分析，我们观察到Toma/TTC-ms对不同细胞类型的不同tau细胞有免疫反应。共定位系数分析表明，病理性tau沉积增加，主要分布在神经元。用TOMA/TTC-MS对脑匀浆进行的Western印迹分析显示，在每种疾病中都有不同的tau聚集模式，这表明TOMA/TTC-ms可以区分不同tau疾病中存在的不同tau聚集体。此外，使用DAPI染色，我们观察到，与非痴呆对照组相比，AD皮质的神经元和星形细胞核的核面积显著增加，染色质致密程度增加。DLB神经元、星形胶质细胞和小胶质细胞、PSP星形胶质细胞和小胶质细胞的核密度/面积减少，染色质疏松。毒性tau在tau病中的细胞类型特异性取向将有助于更好地理解不同脑细胞类型在tau病理中的参与。在本研究中，我们观察到每种疾病都呈现细胞型特异性核表型和tau沉积模式。描述神经退行性疾病中神经元、星形胶质细胞和小胶质细胞的病理tau特征和核变化的示意图。
Accumulation of pathological tau aggregates is a prominent feature in tauopathies that leads during the course of the diseases to neuronal dysfunction before and cell death after. Microglia and astrocytes have been described as playing important roles in synaptic spreading of toxic tau in several neurodegenerative diseases (NDs). Here, we have investigated the immunological and biochemical properties of aggregated tau species in different brain cell types in tau‐induced neurodegenerative diseases such as Alzheimer's disease (AD), progressive supranuclear palsy (PSP), and dementia with Lewy bodies (DLB). Additionally, we examined nuclear size, nuclear density, and chromatin compaction in neuronal and glial cells from diseased brain tissues. Microscopic‐histological examination was performed using in‐house mouse monoclonal antibodies for toxic tau conformers (TTC‐M1 and TTC‐M2) and tau oligomers (TOMA1‐4). By immunohistochemistry and co‐immunofluorescence assays using TOMA/TTC‐Ms and cell‐type specific markers for neurons, astrocytes, and microglia, we observed that TOMA/TTC‐Ms were immunoreactive to diverse tau species in different cell types. Analysis of colocalization coefficients indicated an increased pathological tau deposition mainly in the neurons. Western blot analysis of brain homogenates using TOMA/TTC‐Ms revealed distinct patterns of tau aggregation in each disease, suggesting that TOMA/TTC‐Ms can distinguish between different tau aggregates present in different tauopathies. Additionally, using DAPI staining, we observed that neuronal and astrocytic nuclei had significantly greater nuclear area and increased chromatin compaction in AD cortices compared to non‐demented controls. In contrast, reduction in nuclear density/area and more relaxed chromatin was noticed in DLB neurons, astrocytes and microglia and PSP astrocytes and microglia. Cell‐type specific tropism of toxic tau species in tauopathies will provide a greater understanding of the involvement of different brain cell types in tau pathology. In this study, we observed that each disease presented cell‐type specific nuclear phenotype and tau deposition pattern. Schematic depicting characterization of pathological tau signatures and nuclear alterations in neurons, astrocytes and microglia in neurodegenerative diseases.
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影响因子：
5.3
作者：
Castillo-Carranza, Diana L.;Sengupta, Urmi;Kayed, Rakez
通讯作者：
Kayed, Rakez
影响因子：
16.6
作者：
Jiwaji Z;Tiwari SS;Avilés-Reyes RX;Hooley M;Hampton D;Torvell M;Johnson DA;McQueen J;Baxter P;Sabari-Sankar K;Qiu J;He X;Fowler J;Febery J;Gregory J;Rose J;Tulloch J;Loan J;Story D;McDade K;Smith AM;Greer P;Ball M;Kind PC;Matthews PM;Smith C;Dando O;Spires-Jones TL;Johnson JA;Chandran S;Hardingham GE
通讯作者：
Hardingham GE
DOI：
10.1016/j.mrfmmm.2014.11.010
发表时间：
2015-06-01
影响因子：
2.3
作者：
Coppede, Fabio;Migliore, Lucia
通讯作者：
Migliore, Lucia
DOI：
10.4161/nucl.36289
发表时间：
2014-09
期刊：
Nucleus (Austin, Tex.)
影响因子：
--
作者：
Camozzi D;Capanni C;Cenni V;Mattioli E;Columbaro M;Squarzoni S;Lattanzi G
通讯作者：
Lattanzi G
影响因子：
7.8
作者：
Lee，Min Young;Lee，Junghee;Ryu，Hoon
通讯作者：
Ryu，Hoon